P648: T CELL PHENOTYPIC CHANGES IN PARTICIPANTS OF A MULTIPHASE OPTIMIZATION STRATEGY (MOST) BEHAVIORAL INTERVENTION OF HEALTHY DIET AND EXERCISE IN PATIENTS (PTS) WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
Authors: M. Gordon, J. Crane, C. Y. Lee, S. Fares, K. Basen-Engquist, M. Markofski, A. Ferrajoli, E. LaVoy
Journal: HemaSphere (2022)

Background: Clinical outcomes in pts with CLL are influenced by disease biology, host immune response and comorbidities (Roessner et al, Leukemia, 2020 and Rotbain et al, Leukemia, 2021). Intensive physical exercise can modulate T cell function and slow leukemic progression (Sitlinger et al, Blood Adv., 2020). Here we report baseline and 4 month follow up of T cell phenotype in CLL pts after participation in a MOST exercise program. Aims: Assess the association of comorbidities and T cell subsets in pts with CLL participating in an organized exercise program. Methods: Pts with CLL treated at MD Anderson were randomized to one of 16 combinations of 5 evidence-based behavioral interventions. Pts with baseline and follow up data were included. T cell phenotype was identified by multicolor flow cytometry assessing CD3, CD4, CD8, HLADR and PD1. Difference in baseline and pre/post intervention T cell subset was assessed by t-test and Mann-Whitney. A p-value <.1 was considered significant. Results: Median age was 63 years in the 24 pts with CLL. TP53 aberrancy was present in 8%, unmutated IGHV in 46% and 63% had moderate-severe comorbidities (CLL comorbidity index [CI] score, 1-2). Median prior lines of therapy were 1, 85% were receiving a BTK inhibitor (ibrutinib n=7, acalabrutinib n=2 and zanubrutinib n=2); 50% were untreated. Baseline T cell phenotype showed that a CLL-CI score of 1-2, compared to 0 was associated with lower HLADR+CD4+ T cells (p=.07). CLL-CI score of 1 vs 0 was associated with high PD1+CD8+ T cells (p=.03) and PD1+CD4+ T cells (p=0.06; Fig 1). By individual comorbidity category only upper gastrointestinal comorbidities (n=6) were associated with T cell phenotype, lower HLADR+CD8+ T cells (p=.04). Pts ≥65 years had lower HLADR+CD4+ (p=.04) and HLADR+PD1+CD4+ (p=.09) T cell populations. Advanced Rai stage (2-4) was associated with higher CD8+ T cells (p=.03). Treatment, IGHV and Beta 2 microglobulin were not associated with T cell phenotype. T cell phenotype at 4 months showed that a CLL-CI score of 1-2 vs 0 was associated with lower HLADR+CD4+ T cells (p=.06). Both PD1+CD4+ and PD1+CD8+ T cells were higher in pts with a CLL-CI score of 1 vs 0 (p=.09 for both). Pts with vascular comorbidities had lower CD8+ (p=.09) and higher HLADR+PD1+CD4+ (p=.09) T cells. Endocrine comorbidities were associated with lower HLADR+CD4+ (p=.08) and lower HLADR+PD1+CD4+ (p=.09) T cells. Advanced Rai stage was associate with increased HLADR+CDC8+ T cells (p=.02). Treatment and age did not significantly impact T cell phenotype. Image:Summary/Conclusion: Comorbidities are associated with shorter survival and more rapid progression of CLL (Gordon et al, CCR, 2021 and Rotbain et al, Blood adv., 2022). But the mechanism(s) underlying these observations are not well described. High HLADR+PD1+CD4+ T cells are associated with CLL progression (Elston et al, BJH, 2020). We hypothesized that comorbidities, measured by the CLL-CI, could influence T cell function and thus lead to CLL progression. CLL-CI score was associated T cell phenotype in this study. Pts with comorbidities had higher PD1 expression at baseline. Interestingly, after participation in the exercise intervention, pts with vascular disease had higher HLADR+PD1+CD4+ T cells while those with endocrine comorbidities had lower HLADR+PD1+CD4+ T cells. This suggest that pts with obesity and diabetes may particularly benefit from participation in behavioral interventions by lowering the % of HLADR+PD1+CD4+ T cells.